1. Field of the Invention
The present invention relates to novel chemical compounds and methods for their use in therapy and preparation. In particular, the invention relates to certain substituted quinazoline compounds and to the use for the inhibition, regulation and/or modulation in particular kinase and its related signal transduction.
2. Background Art
Protein kinases (PKs) play important roles in cellular signal pathways that regulate various cell functions such as differentiation, proliferation, migration, survival and apoptosis. These enzymes catalyze the transfer of a phosphate group from ATP to a tyrosine, serine or threonine residue on a protein substrate. The phosphorylation by kinase and dephosphorylation by phosphatase are involved in countless cellular processes that respond to diverse intracellular signals, regulation of cellular functions, and activation or deactivation of cellular operations.
Abnormal PK activity has been linked to cancer as well as metabolic, immunological, and nervous system disorders. Therefore, protein kinases are attractive therapeutic targets for human disease interventions. PK inhibitors, i.e., compounds that block the activities of PKs, have been developed and used widely for clinical applications. While more than thirty PK inhibitors have been approved for use in disease treatments, such as cancer therapy, there is still a need for new PK inhibitors to treat various disorders or to overcome drug-resistance. The identification of effective small molecule compounds that can specifically inhibit signal transduction and cellular proliferation, by modulating PK activity to regulate and modulate inappropriate cell proliferation, differentiation, or metabolism that is essential for processes leading to cancer, would be beneficial.